Molecular alterations in human olfactory mucosal cells from healthy individuals and individuals with Alzheimer's disease induced by real-world ambient air

Environ Toxicol Pharmacol. 2026 Apr 12:124:105019. doi: 10.1016/j.etap.2026.105019. Online ahead of print.

Abstract

Ambient air pollution is a global problem linked to various diseases, including neurodegenerative disorders. Using a mobile exposure system, we investigated the molecular changes in human olfactory cleft mucosal (hOM) cells from healthy individuals and Alzheimer's disease (AD) patients exposed to real-world ambient air. Samples were exposed at the air-liquid interface in a low-pollution Background site and a moderately polluted (within recommended limits) Industrial site. We assessed immune response-related molecules, lipid peroxidation and global RNA expression. Leukemia-inhibitory factor (LIF) increased in healthy, but not AD samples at the Industrial locality, while lipid peroxidation levels remained unchanged. Compared with a blank control, significant enrichment of biological processes and KEGG pathways occurred only in Industrial site samples. In healthy cells, neurodegeneration-related pathways were significantly affected, whereas AD samples showed enhanced inflammation-related responses. These findings suggest that even pollution within recommended limits can induce molecular changes potentially contributing to neurodegenerative disease development.

Keywords: Air pollution; Alzheimer's disease; Exposure; Olfactory cleft mucosal cells.